Prognostic factors for improvement of shoulder function after arthroscopic rotator cuff repair: a systematic review

Background The identification of factors that specify prognostic models for postoperative results should be based on the best scientific evidence and expert assessment. We aimed to identify, map, and evaluate potential prognostic factors for the improvement of shoulder function in patients undergoing arthroscopic rotator cuff repair. Methods Longitudinal primary studies of arthroscopic rotator cuff repair reporting any multivariable factor analyses for shoulder function improvement with an endpoint assessment of at least 6 months were included. We systematically searched EMBASE, Medline, and Scopus for articles published between January 2014 and June 2021. The risk of bias of included studies and the quality of evidence were assessed using the Quality in Prognosis Studies tool and an adapted Grading of Recommendations, Assessment, Development, and Evaluations framework. Results Overall, 24 studies including 73 outcome analyses were included. We classified younger age and smaller tear size as probably prognostic for a greater improvement in objective outcomes. Shorter symptom duration, absence of a worker compensation claim, low preoperative level of functional status, and high preoperative pain level were classified as probably prognostic for greater improvement in patient-reported outcome measures. The quality of the synthesized evidence was low. Twenty-one studies had an overall high risk of bias. Conclusion Six potential prognostic factors for shoulder function after arthroscopic rotator cuff repair were identified. Along with ongoing expert opinion assessments, they will feed into a prognostic model-building process.


Methods
The present review was written according to the updated Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. 52 The protocol was registered in PROSPERO on August 24, 2020 (registration number: CRD42020199257). Detailed methods were described elsewhere. 64 Briefly, longitudinal primary studies of adult patients who underwent primary ARCR that reported on multivariable factor analyses for shoulder function improvement with an endpoint assessment of at least 6 months were included. Shoulder function outcomes were classified as objective outcomes (including muscle strength and range of motion parameters), or patient-reported outcome measures (PROMs) (including all the patient-reported shoulder function scales, such as the American Shoulder and Elbow Surgeons (ASES) 45 scale, the Constant-Murley 11 score, the Simple Shoulder Test 41 (SST), University of California Los Angeles 1 shoulder score, the Western Ontario Rotator Cuff (WORC) 31 score and its short version (short WORC), 16 the Oxford Shoulder Score, 13 the Japanese Orthopedic Association or the visual analog scale (VAS) for shoulder pain).
A systematic search was run in EMBASE (Elsevier), Medline (Ovid), and Scopus for articles published between 2014 and June 9, 2021 (see Supplemental File 1). Search results were limited to 2014 and onward, since surgical rotator cuff repairs substantially evolved in 2013/2014. 14 To complement the results of database searching, we implemented a screening of all the included references as well as the citing articles of those indexed in Scopus or the Web of Science (June 10, 2021). The bibliographic references of identified topical systematic reviews and research articles were also screened as an additional source.
Two screening phases based on titles and abstracts and fulltexts, respectively, were performed independently by two authors (TS, LM) and involved the judgment of a senior author (LA), when necessary. Data extraction and risk of bias assessment using the Quality in Prognosis Study tool 28 were performed independently by pairs of two authors (TS, LM, ML, and RL). Data extraction items were based on an adaptation of the Checklist for Critical Appraisal and data extraction for systematic reviews of prediction modeling studies for prognostic factors (see Supplemental File 2). 46 Effect estimates were reported as described in individual studies. The quality of the synthesized evidence was graded according to an adaptation of the Grading of Recommendations, Assessment, Development, and Evaluations framework applied to prognostic factors findings. 33 Potential prognostic factors were then narratively synthesized in the Results section when the quality of the evidence was "Low." We raised the quality assessment of the synthesized evidence when 50% or more of the studies reported the same direction for an association between a given factor and its outcome.
Based on this quality assessment, factors were then categorized into patient-related, disease-related, and procedure-related factors with potential prognostic value or as requiring further analyses.
Due to heterogeneity in reported outcomes and prognostic factor definitions, we were not able to perform meta-analysis as originally planned during review registration.

Prognostic factors for objective outcomes
Overall, 23 potential prognostic factors for objective outcomes were identified and included 12 patient-related factors, 7 diseaserelated factors, and 4 procedure-related factors (Table III and see  Supplemental Table 3a).

Younger age
Two studies reported significant associations between age and postoperative objective outcomes. The first study reported a multivariable test result for dichotomized age categories of smaller than 55 years old or greater than 55 years old, which indicated that increasing age was significantly associated with worse postoperative objective outcome (P < .0001). 20 The second study reported a regression coefficient (b) of À0.227 (P ¼ .008) 61 for increasing age that was kept as a continuous factor (Table III and see  Supplemental Table 3). Both results suggested that younger age was associated with greater improvement in postoperative objective outcomes.

Smaller tear size
Results from two studies suggested that smaller tear size was associated with greater improvement in postoperative objective outcomes; when described as the largest tear dimension measured intraoperatively and categorized as small (less than 1 cm), medium (1 to 3 cm), and large (3 to 5 cm), authors reported a significant multivariable association (P < .0001) 20 and, when kept continuous and expressed as area (in cm2), authors reported a regression coefficient of b ¼ À0.332 for increasing tear size (P ¼ .006). 61

Prognostic factors for PROMs
Overall, 48 potential prognostic factors were identified including 12 patient-related factors, 18 disease-related factors, and 18 procedure-related factors (Table IV and see Supplemental  Table 3b).

Shorter symptom duration
Five studies reported associations between symptom duration and postoperative PROMs. 18,19,25,36,51 Six multivariable outcomefactor analyses (50%) reported a significant association. One study reported a 19-point better improvement in Constant Score at 12 months (b ¼ 19.4; P < .001) in patients undergoing the operation within 3 months after symptom onset compared to other patients. 19 In another study, performing the operation within 3 months after symptom onset was associated with a 3-times higher odds (odds ratio ¼ 3.1; 95% confidence interval 1.1 to 8.6; P ¼ .028) to achieve a patient acceptable symptom state corresponding to a value of 1.7 points in VAS shoulder pain. 36 In the third study, three outcome analyses were reported, a repair within 4 months after symptom onset resulted in 10.3 points improvement in 24 months ASES (P ¼ .008), 1.8 points in 24 months SST (P ¼ .001), 8.6 points improvement in Subjective Shoulder Value (P ¼ .033), and 0.93 points improvement in pain VAS scale (P ¼ .028). 25 One study reported a trend of less improvement in shoulder function after longer symptom duration without reaching statistical significance on multivariable analysis. 18 Altogether, these results suggested that shorter symptom duration was associated with greater improvement in PROMs.

Absence of a worker's compensation claim
Six studies reported associations between the worker's compensation claim status and PROMs. 4,12,20,25,51,68 Of the 20 outcome-factor analyses reported, 9 (45%) multivariable associations were reported. 4,12,20,25 One study reported an association between the presence of a worker's compensation claim and worse postoperative Constant Score, short WORC, and ASES at 24 months (P < .0001). 20 Two studies reported significant odds ratio suggesting the presence of a worker's compensation claim was associated with worse improvement in PROM. 4,12 One study reported a 11-point lower ASES at 12 months in patients with a worker's compensation claim (b ¼ À11.1; P ¼ .019). 25 Three multivariable associations were, however, not statistically significant (P ¼ .061 for postoperative 24 months SST score, P ¼ .071 for postoperative 24 months Subjective Shoulder Value score, and P ¼ .055 for postoperative 24 months VAS pain score). 25 These results suggested that the presence of a worker's compensation claim was associated with lower improvement in PROMs.

Worse preoperative functional status
Associations between baseline levels of functional status or pain level were studied in 36 analyses across nine studies, 12,20,25,27,36,37,43,49,51 17 analyses reported significantly lower shoulder function improvement in patients with higher preoperative functional status 12,25,27,37,43 and 4 analyses reported significant associations between higher preoperative pain level and better postoperative PROMs. 36,37,49 The synthesized results indicated that worse preoperative functional status (including higher baseline pain levels) was associated with greater improvement in PROMs.

Quality of the synthesized evidence
The overall quality of the evidence was low to very low. Nonetheless, younger age and smaller tear size were classified as probably prognostic for greater improvement in objective functional outcomes, yet with a low quality of evidence (Table III). Shorter symptom duration, absence of a worker compensation claim, and worse baseline functional status (including higher baseline pain levels) were classified as probably prognostic for greater improvement in PROMs (Table IV). The quality of the synthesized evidence on prognostic factor findings was notably affected by the absence of a full reporting of prognostic factor estimates.

Risk of bias
Three studies (12.5%) had an overall moderate risk of bias 25,37,69 with the remaining studies judged as having an overall high risk of bias (Fig. 2, see Supplemental Table 4). This assessment was notably impacted by the item "Statistical Analysis and Reporting," mostly due to a lack of appropriate multivariable and univariable effect estimates reporting.

Multivariable modeling phase
Only studies with a low or moderate risk of bias in the item "Statistical Analysis and Reporting" were considered in this section, representing 7 studies (29.1%) and 32 outcome analyses 4,6,12,25,37,48,69 (Table V and see Supplemental Table 5). Some working groups included all the initial factors presented in their analyses in the reported multivariable models, 25,48,69 whereas others included factors in their reported multivariable models on the basis of significant univariable 12,36 or multivariable analyses 6 (29% and 14%, respectively). Lastly, one study (4%) reported a performance indicator for their presented model based on the Hosmer-Lemeshow goodness of fit test. 37

Discussion
The objective of the present review was to identify, map, and evaluate potential prognostic factors for the improvement of shoulder function in patients undergoing ARCR. We classified younger age and a smaller tear size as probable prognostic factors for greater improvement in objective outcomes. The absence of a worker compensation claim, shorter symptom duration, and worse baseline functional status (including higher preoperative levels of pain) was classified as probable prognostic factors for greater improvement in PROM.

General interpretation of the results in the context of other evidence
During the preparation of our manuscript, a confirmatory systematic review and meta-analysis with slightly different inclusion criteria was published, reporting that prospective ARCR studies with lower mean outcome values at baseline and smaller tear sizes were associated with better clinical outcomes. 32 Other systematic review authors reported the existence of a correlation between poor baseline psychological function and worsening postoperative PROM 53 and identified a wide variety of prognostic factors for functional clinical outcomes, but also conflicting evidence and low methodological quality of included studies. 21,39,44,57,63 Still, Fermont et al concluded that younger age and smaller tear size was associated with better recovery, 21 but could not classify the duration of symptoms as a prognostic factor. Lambers Heerspink et al identified increased age and larger tear size as negative predictors of functional status recovery, and the presence of a worker's compensation claim as having a negative influence on functional outcomes. Again, however, duration of symptoms could not be classified as being prognostic due to limited evidence. 39 Yet, Higher preoperative functional scores 27,31,33,34,36,37,40 Higher preoperative pain level 35,36,39,40 Acromion type 41 Dominance affected side 25,27,37,40 Concomitant rotator cuff pathologies 31 Cuff tear index 38 Fatty infiltration 26,32,38,40 Preoperative muscle strength 40 Preoperative range of motion 32,39 Postoperative shoulder stiffness 35 Postoperative retear 36 Synovitis 35 Tear location 29,30 Tear pattern 25,27,35,36 Tear retraction 26,32,37,40,42 Tear shape 47 Tear size [26][27][28][29]31,[33][34][35][36][40][41][42]46,47 Traumatic onset 29,30,40,45 Procedure-related Acromioclavicular joint procedures 27,41 Acromioplasty [35][36][37]41 Biceps procedure [25][26][27]36,37,40,41 Concomitant procedures 30 Follow-up duration 40 Infraspinatus repair 37 Lateral debridement 27 Mobilization 27 Number of anchors 26,28 Preoperative corticosteroid injections 29 Preoperative physical therapy 29,30 Posterosuperior tear repair 41 Procedure location 26 Repair technique 26,27,36 Subscapularis repair 26,37 Supraspinatus repair 37 Surgeon effect 28 Timing of preoperative corticosteroid injection 30 duration of symptoms is a known predictor for worse baseline outcome status, indicating the confounding nature of this factor for baseline status. 38 Such a factor should therefore be considered when describing baseline associations. McElvany et al reported that older patients and larger tears have an increased risk of failure of rotator cuff repair. 44 Raman et al also reported a negative effect of larger tear size, increasing age, and worker's compensation claim status on ARCR outcomes, 57 but, again, the authors did not find a significant influence of symptom duration. Saccomanno et al reported that retear risk is affected by older age and larger tear size and that baseline scores and work compensation claims were the most significant predictors for functional outcomes. 63 Taken together, our findings on prognostic factors are supported by similar previous reviews, with the notable exception of symptom duration, which was not identified by other systematic reviewers, probably due its confounding nature and to the heterogeneity in the sets of factors used to model postoperative outcomes.

Modeling changes in functional outcomes
We defined an improvement in outcomes as an improvement in outcomes at a patient level, regardless of whether the reviewed studies focused on the achievement of minimal clinical important difference, the achievement of a patient acceptable symptom state or substantial clinical benefit, or whether postoperative values were modeled. Both indicators were relevant in our context because we aimed to identify blocks of factors influencing the change over time or postoperative values. However, we are aware of the impact that ceiling effects and preoperative functional status impact the achievement of minimal clinical important difference. 50 When considering interpretable outcomes taking into consideration preoperative patient functional status, the use of a new indicator such as the maximal outcome improvement might be of importance, as defined by Beck et al. 4 The benefits of the use of maximal outcome improvement are that a satisfactory outcome can be determined even for patients with high preoperative function and the challenges of ceiling effects restricted, especially when predicting interpretable outcomes for individual patients. 67 Limitations of the review processes used Our review was limited by our choice to only analyze original articles published in English, German, and French. The risk of bias regarding the statistical analysis and reporting item was notably affected by the selective reporting of the included studies and focus on reporting only point effect estimates for significant associations. We would have expected the transparency of all univariable and multivariable regression coefficients to ensure a better understanding of the underlying associations between factors and outcomes. When published studies only report significant associations (at a P < .05 threshold), meaningful information regarding notable factors of estimated direction and strength of associations is missed. Having access to detailed and informative results might have permitted a meta-analysis on a given outcome for a given time point, yet this appeared inappropriate in the context of our review.

Implications of the results for practice, policy, and future research
To improve current standards in the field, recommendations and a general framework for prognostic studies have been made. 29 To improve the quality of reporting multivariable prognostic models, we foster the use of well-designed guidelines from the EQUATOR network group, such as the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statement. 10 The results of our review are transferrable to the clinical setting and support the optimal decision-making process for surgery for a given patient. When aiming to achieve greater improvement after elective orthopedic surgery, a poor baseline patient status is usually a good indicator of success for improvement over time. However, this association is only observed for improvement in PROMs. In contrast, objective functional outcome measurements seem to decrease with greater tear size and older age. The same factors were shown to be associated with decreased tendon healing, 44 which was found to be a relevant factor for the functional outcome, particularly for strength recovery. 62 In clinical practice, patients with larger tear sizes and older age may therefore expect subjective recovery if their baseline PROMs are low, but they should be  Significant on multivariable analysis 1 (14) 6 Stepwise regression 1 (14) 4 All factors were included 3 (43) 25,48,69 Presented model performance indicators None 6 (86) 4,6,12,25,48,69 Hosmer-Lemeshow test 1 (14) 37 informed about limited functional improvements following ARCR and a high risk of retears. Namely, these patients may only be good candidates for ARCR if they have poor PROMs (particularly due to pain) with acceptable shoulder function. In contrast, surgery should not be delayed for young patients with small tear sizes given the high chances of functional improvement and potential negative effects of prolonged symptom duration.

Conclusion
Six potential prognostic factors for shoulder function improvement were identified. Their prognostic value should be confirmed by expert assessment. The results of the present review are the initial step toward developing prediction models in ARCR outcomes as part of our ARCR_Pred cohort study. 2

Disclaimers:
Funding: This literature search is supported by the Swiss National Science Foundation, Switzerland Grant ID 320030_184959/1. Conflicts of interest: The authors, their immediate families, and any research foundation with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.